Up-regulation of the ectodermal-neural cortex 1 (ENC1) gene, a downstream target of the beta-catenin/T-cell factor complex, in colorectal carcinomas

Cancer Res. 2001 Nov 1;61(21):7722-6.

Abstract

To clarify the molecular mechanisms of human carcinogenesis associated with abnormal Wnt/wingless signaling, we searched for genes the expression of which was significantly altered by introduction of wild-type AXIN1 into LoVo colon cancer cells. By means of a cDNA microarray, we compared expression profiles of LoVo cells infected with either adenoviruses expressing wild-type AXIN1 (Ad-Axin) or those expressing a control gene (Ad-LacZ). Among the genes showing altered expression, the ectodermal-neural cortex 1 (ENC1) gene was down-regulated in response to Ad-Axin. The promoter activity of ENC1 was elevated approximately 3-fold by transfection of an activated form of beta-catenin together with wild-type T-cell factor (Tcf)4 in HeLa cells. Semiquantitative reverse transcription-PCR experiments revealed that expression of ENC1 was increased in more than two-thirds of 24 primary colon cancer tissues that we examined compared with corresponding noncancerous mucosae. Introduction of exogenous ENC1 increased the growth rate of HCT116 colon cancer cells in serum-depleted medium. In other experiments, overexpression of ENC1 in HT-29 colon cancer cells suppressed the usual increase of two differentiation markers, in response to treatment with sodium butyrate, a differentiation-inducible agent. These data suggest that ENC1 is regulated by the beta-catenin/Tcf pathway and that its altered expression may contribute to colorectal carcinogenesis by suppressing differentiation of colonic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axin Protein
  • Butyrates / pharmacology
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cytoskeletal Proteins / biosynthesis
  • Cytoskeletal Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Microfilament Proteins / biosynthesis
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / physiology
  • Neuropeptides / biosynthesis
  • Neuropeptides / genetics*
  • Neuropeptides / physiology
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology
  • Promoter Regions, Genetic
  • Proteins / genetics
  • Repressor Proteins*
  • TCF Transcription Factors
  • Trans-Activators*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transduction, Genetic
  • Transfection
  • Tumor Cells, Cultured
  • Up-Regulation
  • beta Catenin

Substances

  • AXIN1 protein, human
  • Axin Protein
  • Butyrates
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Microfilament Proteins
  • Neuropeptides
  • Nuclear Proteins
  • Proteins
  • Repressor Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Trans-Activators
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • beta Catenin
  • ectodermal-neural cortex 1 protein